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Gert Holstege

Publications and source records attributed to Gert Holstege.

At least 19 recordsLinked to original sources
PubMed2006

Afferent projections to the pontine micturition center in the cat.

The pontine micturition center (PMC) or Barrington's nucleus controls micturition by way of its descending projections to the sacral spinal cord. However, little is known about the afferents to the PMC that control its function and may be responsible for dysfunction in patients with urge-incontinence and overactive bladder. In five female cats, wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections were made in the PMC and adjoining dorsolateral pontine tegmentum. Retrogradely labeled neurons were found in a large area, including the medullary and pontine medial and lateral tegmental field; dorsomedial, lateral, and ventrolateral periaqueductal gray matter (PAG); posterior hypothalamus; medial preoptic area (MPO); bed nucleus of the stria terminalis; central nucleus of the amygdala; and infralimbic, prelimbic, and insular cortices. To verify whether these areas indeed project specifically to the PMC or perhaps only to adjacent structures in the pontine tegmentum, in 67 cats (3)H-leucine or WGA-HRP injections were made in each of these regions. Five cell groups appeared to have direct connections to the PMC, the ventromedial pontomedullary tegmental field, the ventrolateral and dorsomedial PAG, the MPO, and the posterior hypothalamus. The possible functions of these projections are discussed. These results indicate that all other parts of the brain that influence micturition have no direct connection with the PMC.

Afferent Pathways↗
PubMed2006

Periparabigeminal and adjoining mesencephalic tegmental field projections to the dorsolateral periaqueductal grey in cat - a possible role for oculomotor input in the defensive system.

The dorsolateral column of the mesencephalic periaqueductal grey (PAGdl) differs from its adjacent columns in terms of afferent and efferent connections and the distribution pattern of different histochemical substances. Functionally, PAGdl is associated with aversive and defensive behaviours, but in an earlier study of this laboratory [E.M. Klop et al. (2005) J. Comp. Neurol., 492, 303-322], it was found that PAGdl specifically receives input from the nucleus prepositus hypoglossi, which plays a role in oculomotor control. In search for other oculomotor-related brainstem structures projecting to PAGdl we studied the projections from the parabigeminal nucleus (PBGN) and its medially adjoining periparabigeminal area (PPBGA). In three cats, injections of wheatgerm agglutinin-horseradish peroxidase involving PAGdl did not, or to only a very limited extent, result in retrogradely labelled neurons in PBGN. When the peripheral parts of PAGdl were involved in the injection site, labelled neurons were located in PPBGA, while after an injection involving only the more central parts of PAGdl they were located in the tegmentum medial to the PPBGA. An anterograde tracing study using [3H]-leucine and biotinylated dextran amine affirmed that neurons in PPBGA project to more peripheral parts of PAGdl, while neurons located in the tegmentum medial to PPBGA project mainly to its central parts. These results provide further evidence for the existence of two different subdivisions of PAGdl. We hypothesize that PAGdl is alerted by sudden changes in the visual field, and that the PAGdl defensive system is inhibited when these changes are caused by eye movements.

Animals↗
PubMed2006

Infralimbic cortex projects to all parts of the pontine and medullary lateral tegmental field in cat.

The infralimbic cortex (ILc) in cat is the ventralmost part of the anterior cingulate gyrus. The ILc, together with the amygdala, bed nucleus of the stria terminalis and lateral hypothalamus, is involved in the regulation of fear behavior. The latter three structures are thought to take part in triggering the fear response by means of their projections to the pontine and medullary lateral tegmental field (LTF). The LTF is a large region extending from the parabrachial nuclei rostrally to the spinal cord caudally. It contains almost all the premotor interneurons for the brainstem and for some upper spinal cord motoneurons innervating the muscles of face, head and throat. The question is whether ILc also projects to the LTF. Such a pathway would allow the ILc to influence the fear response by acting directly on these premotor interneurons. Anterograde tracer injections were made in the medial surface of the cortex in four cats. Only when the injection sites involved ILc were anterogradely labeled fibers observed throughout the rostrocaudal extent of the LTF. To verify whether these projections indeed originated from ILc, in two other cases retrograde tracer injections were made in the pontomedullary LTF. The results showed many retrogradely labeled neurons in ILc, but none in adjacent cortical regions. These results show that the ILc projects to the LTF in cat and can possibly modulate the fear response not only via indirect but also via direct routes to the premotor interneurons in the brainstem.

Animals↗
PubMed2006

Regional cerebral blood flow changes associated with clitorally induced orgasm in healthy women.

There is a severe lack of knowledge regarding the brain regions involved in human sexual performance in general, and female orgasm in particular. We used [15O]-H2O positron emission tomography to measure regional cerebral blood flow (rCBF) in 12 healthy women during a nonsexual resting state, clitorally induced orgasm, sexual clitoral stimulation (sexual arousal control) and imitation of orgasm (motor output control). Extracerebral markers of sexual performance and orgasm were rectal pressure variability (RPstd) and perceived level of sexual arousal (PSA). Sexual stimulation of the clitoris (compared to rest) significantly increased rCBF in the left secondary and right dorsal primary somatosensory cortex, providing the first account of neocortical processing of sexual clitoral information. In contrast, orgasm was mainly associated with profound rCBF decreases in the neocortex when compared with the control conditions (clitoral stimulation and imitation of orgasm), particularly in the left lateral orbitofrontal cortex, inferior temporal gyrus and anterior temporal pole. Significant positive correlations were found between RPstd and rCBF in the left deep cerebellar nuclei, and between PSA and rCBF in the ventral midbrain and right caudate nucleus. We propose that decreased blood flow in the left lateral orbitofrontal cortex signifies behavioural disinhibition during orgasm in women, and that deactivation of the temporal lobe is directly related to high sexual arousal. In addition, the deep cerebellar nuclei may be involved in orgasm-specific muscle contractions while the involvement of the ventral midbrain and right caudate nucleus suggests a role for dopamine in female sexual arousal and orgasm.

Adult↗
PubMed2005

Segmental and laminar organization of the spinothalamic neurons in cat: evidence for at least five separate clusters.

The spinothalamic tract (STT), well known for its role in the relay of information about noxe, temperature, and crude touch, is usually associated with projections from lamina I, but spinothalamic neurons in other laminae have also been reported. In cat, no complete overview exists of the precise location and number of spinal cells that project to the thalamus. In the present study the laminar distribution of retrogradely labeled cells in all spinal segments (C1-Coc2) was investigated after large WGA-HRP injections in the thalamus. The results show that this distribution of STT cells differed greatly between the different spinal segments. Quantitative analysis showed that there exist at least five separate clusters of spinothalamic neurons. Lamina I neurons in cluster A and lamina V neurons in cluster B are mainly found contralaterally throughout the length of the spinal cord. Cluster C neurons are located bilaterally in the ventrolateral part of laminae VI-VII and lamina VIII of the C1-C3 spinal cord. Cluster D neurons were found contralaterally in lamina VI in the C1-C2 segments, and cluster E neurons were located mainly contralaterally in the medial part of laminae VI-VII and lamina VIII of the lumbosacral cord. Most spinothalamic neurons are not located in the enlargements and most spinothalamic neurons are not located in lamina I, as suggested by several other authors. The location of the spinothalamic neurons shows remarkable similarities, but also differences, with the location of spino-periaqueductal gray neurons.

Animals↗
PubMed2005

Human brain activation during sexual stimulation of the penis.

Penile sensory information is essential for reproduction, but almost nothing is known about how sexually salient inputs from the penis are processed in the brain. We used positron emission tomography to measure regional cerebral blood flow (rCBF) during various stages of male sexual performance. Compared to a passive resting condition (without penile erection), sexual stimulation of the penis increased rCBF in an area of the right hemisphere encompassing the posterior insula and adjacent posterior part of the secondary somatosensory cortex (SII) and decreased rCBF in the right amygdala. No activation was observed in either the thalamus, genital part of primary somatosensory cortex (SI), or hypothalamus. Based on these results we put forward the concept that during sexual performance the salience of the stimulus, represented by activation of the insula and SII, is of greater significance than the exact location of the stimulus, encoded in SI. The absence of activation in the hypothalamus indicates that this region is more important for the onset of sexual arousal than for the resulting sexual performance. Deactivation of the amygdala during sexual stimulation of the penis corresponds with a decrease of vigilance during sexual performance.

Adult↗
PubMed2005

Micturition and the soul.

There is a close connection between micturition and emotion. Several species use micturition to signal important messages as territorial demarcation and sexual attraction. For this reason, micturition is coordinated not in the spinal cord but in the brainstem, where it is closely connected with the limbic system. In cat, bladder afferents terminate in a cell group in the lateral dorsal horn and lateral part of the intermediate zone. Neurons in this cell group project to supraspinal levels, not to the thalamus but to the central periaqueductal gray (PAG). Neurons in the lateral PAG, not receiving direct sacral cord afferents, project to the pontine micturition center (PMC). The PMC projects directly to the parasympathetic bladder motoneurons and to sacral GABA-ergic and glycinergic premotor interneurons that inhibit motoneurons in Onuf's nucleus innervating the external striated bladder sphincter. Thus, PMC stimulation causes bladder contraction and bladder sphincter relaxation, i.e., complete micturition. Other than the PAG, only the preoptic area and a cell group in the caudal hypothalamus project directly to the PMC. The ventromedial upper medullary tegmentum also sends projections to the PMC, but they are diffuse and also involve structures that adjoin the PMC. Neuroimaging studies in humans suggest that the systems controlling micturition in cat and human are very similar. It seems that the many structures in the brain that are known to influence micturition use the PAG as relay to the PMC. This basic organization has to be kept in mind in the fight against overactive bladder (OAB) and urge-incontinence.

Animals↗
PubMed2005

Two parts of the nucleus prepositus hypoglossi project to two different subdivisions of the dorsolateral periaqueductal gray in cat.

The dorsolateral column of the mesencephalic periaqueductal gray (PAG) is a separate part of the PAG. Its afferent sources, efferent targets, and neurochemical properties differ from the adjacent PAG columns. The dorsolateral PAG is thought to be associated with aversive behaviors, but it is not yet understood how these behaviors are brought about. To elucidate the function of the PAG further, in the present study we investigated which brainstem regions project to the dorsolateral PAG. Wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injections involving the dorsolateral PAG, but extending into the lateral part, resulted in many retrogradely labeled cells in the pontine and medullary tegmentum bilaterally. However, it was concluded that these neurons were labeled from the lateral PAG, because no anterograde labeling was found in the dorsolateral PAG after a large injection into the tegmentum. Retrogradely labeled cells were also found in the nucleus prepositus hypoglossi (PPH), mainly contralaterally. Injections of [3H]leucine or WGA-HRP in the PPH resulted in anterogradely labeled fibers in the dorsolateral PAG. Two separate distribution patterns were found. The caudal and intermediate PPH projected to a small region on the dorsolateral edge of the dorsolateral column, whereas the supragenual PPH distributed labeled fibers to all other parts of the dorsolateral PAG, except the area on the dorsolateral edge. These separate PPH projections suggest that two subdivisions exist within the dorsolateral PAG. The present findings suggest a role for the dorsolateral PAG in the oculomotor system.

Animals↗
PubMed2005

Afferent projections to pharynx and soft palate motoneurons: a light and electron microscopical tracing study in the cat.

Pharynx and soft palate are muscles for respiration, vocalization, swallowing, and vomiting. In cat, motoneurons innervating pharynx/soft palate are located in the dorsal group of the nucleus ambiguus (dgNA) in the medulla oblongata. In cat, dgNA is the only part of nucleus ambiguus that can be distinguished as a separate cell group, which makes it possible to study its afferent input. In two cats, WGA-HRP injections in dgNA and surrounding tegmentum resulted in retrogradely labeled cells at several levels of the neuraxis. In 170 cases anterograde tracers were injected in areas in which the cells of origin were identified. Results demonstrate that dgNA afferents originate from the tegmentum dorsolateral to the superior olivary complex, medullary ventromedial tegmentum, caudal raphe nuclei, medullary lateral tegmental field, nucleus retroambiguus (NRA), and adjoining tegmentum, extending into the first cervical segment of the spinal cord. In order to determine whether periaqueductal gray (PAG) and parabrachial nuclei (PB) make synaptic contacts with dgNA, ultrastructural studies combined anterograde tracing from PAG, PB, and NRA with retrograde tracing of pharyngeal and soft palate motoneurons. The results showed that PB, but not PAG, projects to the dgNA and that NRA afferent synapses are three times as numerous as those from PB. The morphology of PB and NRA synapses is consistent with excitatory input. In conclusion, pharyngeal and soft palate motoneurons receive their afferents almost exclusively from the pontine and medullary tegmentum and first cervical spinal segment.

Animals↗
PubMed2005

C1-C3 spinal cord projections to periaqueductal gray and thalamus: a quantitative retrograde tracing study in cat.

By far, the strongest spinal cord projections to periaqueductal gray (PAG) and thalamus originate from the upper three cervical segments, but their precise organization and function are not known. In the present study in cat, tracer injections in PAG or in thalamus resulted in more than 2400 labeled cells, mainly contralaterally, in the first three cervical segments (C1-C3), in a 1:4 series of sections, excluding cells in the dorsal column and lateral cervical nuclei. These cells represent about 30% of all neurons in the entire spinal cord projecting to PAG and about 45% of all spinothalamic neurons. About half of the C1-C3 PAG and C1-C3 thalamic neurons were clustered laterally in the ventral horn (C(1-3vl)), bilaterally, with a slight ipsilateral preponderance. The highest numbers of C(1-3vl)-PAG and C(1-3vl)-thalamic cells were found in C1, with the greatest density rostrocaudally in the middle part of C1. A concept is put forward that C(1-3vl) cells relay information from all levels of the cord to PAG and/or thalamus, although the processing of specific information from upper neck muscles and tendons or facet joints might also play a role.

Animals↗
PubMed2005

Central nervous system control of ejaculation.

An overview is given of the regions in the spinal cord that are active during ejaculation. Motoneurons involved are the preganglionic sympathetic motoneurons in the upper lumbar spinal cord and the motoneurons in the nucleus of Onuf, located in the upper sacral cord. The first group is involved in the so-called emission phase of ejaculation, the last group in the expulsion phase. Both groups receive afferents from premotor interneurons in the so-called intermediomedial cell groups located at about the same level as the motoneurons themselves. A concept is put forward in which these premotor cell groups represent the central spinal pattern generators for ejaculation, one for the emission phase and one for the expulsion phase. Clinical observations in patients suffering from transection of the spinal cord indicate that the ejaculation motoneurons as well as their spinal central pattern generators are under strong influence of descending pathways originating in supraspinal parts of the brain. The various pathways possibly involved in ejaculation control are reviewed. Finally, the results of the brain activation of a PET-scan study in human males, ejaculating after penile stimulation by their female partner are discussed. Especially the ventral tegmental area and the cerebellum seem to be activated during ejaculation, while the amygdala region is deactivated. Apparently, a general lack of fear is necessary for ejaculation to occur.

Animals↗
PubMed2005

Neurons in the lateral sacral cord of the cat project to periaqueductal grey, but not to thalamus.

Previous work of our laboratory has shown that neurons in the lateral sacral cord in cat project heavily to the periaqueductal grey (PAG), in all likelihood conveying information from bladder and genital organs. In humans this information usually does not reach consciousness, which raises the question of whether the lateral sacral cell group projects to the thalamus. After wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) injections into the sacral cord, anterogradely labelled fibers were found in the thalamus, specifically in the ventral anterior and ventral lateral nuclei, the medial and intralaminar nuclei, the lateral ventrobasal complex/ventroposterior lateral nucleus, and the nucleus centre median, lateral to the fasciculus retroflexus. Much denser projections were found to the central parts of the PAG, mainly to its dorsolateral and ventrolateral parts at caudal levels and lateral parts at intermediate levels. In a subsequent retrograde tracing study, injections were made in those parts of the thalamus that received sacral fibers, as found in the anterograde study. Labelled neurons were observed in the sacral cord, but not in the lateral sacral cell group. In contrast, a small control injection in the caudal PAG resulted in many labelled neurons in the lateral sacral cord. These results suggest that afferent information regarding micturition and sexual behaviour is relayed to the PAG, rather than to the thalamus.

Afferent Pathways↗
PubMed2004

Ultrastructural evidence for a direct excitatory pathway from the nucleus retroambiguus to lateral longissimus and quadratus lumborum motoneurons in the female golden hamster.

During mating, the female golden hamster displays a stereotyped specific receptive posture, characterized by lordosis of the back, elevation of the tail, and extension of the legs. Muscles involved in this posture are thought to be iliopsoas, cutaneus trunci, lateral longissimus (LL), and quadratus lumborum (QL). Lesion studies in rats suggest that mating behavior is controlled by the mesencephalic periaqueductal gray (PAG). The PAG does not project directly to the motoneurons innervating the muscles involved in mating, but is thought to make use of the nucleus retroambiguus (NRA) as relay. The NRA is located ventrolaterally in the most caudal medulla, and projects directly to iliopsoas and cutaneus trunci motoneuronal cell groups. The question is whether this is also true for LL and QL muscles. Retrograde HRP tracing experiments revealed that LL and QL motoneurons are located medially in the ventral horn of the T12-L6 and T13-L4 segments, respectively. A subsequent ultrastructural study combined wheatgerm agglutinin-conjugated horseradish peroxidase injections in the NRA with cholera-toxin B-subunit injections in LL and QL muscles. The results revealed monosynaptic contacts between anterogradely labeled NRA-fiber terminals with retrogradely labeled dendrites of both LL and QL motoneurons. Almost all these terminals had asymmetrical synapses and contained spherical vesicles, suggesting an excitatory function of this NRA-motoneuronal pathway. These results correspond with the hypothesis that in hamster the PAG-NRA-motoneuronal projection not only involves motoneurons of iliopsoas and cutaneus trunci but also of LL and QL.

Animals↗
PubMed2004

Location of bladder and urethral sphincter motoneurons in the male guinea pig (Cavia porcellus).

Although the guinea pig is used widely in experimental medical research, including in studies on micturition control, the spinal origin of preganglionic parasympathetic bladder and somatic external urethral sphincter motoneurons is not known. In the male guinea pig using wheat germ agglutinin-conjugated horseradish peroxidase and dextran Alexa Fluor 488/568 tracers, preganglionic parasympathetic bladder motoneurons were observed in the ventrolateral part of the intermediolateral cell group of the first sacral segment. The external urethral sphincter motoneurons were found to be located in the ventral horn of the first sacral segment, in a cell group corresponding with the nucleus of Onuf in cat and human.

Animals↗
PubMed2004

Lateral cervical nucleus projections to periaqueductal gray matter in cat.

The midbrain periaqueductal gray matter (PAG) integrates the basic responses necessary for survival of individuals and species. Examples are defense behaviors such as fight, flight, and freezing, but also sexual behavior, vocalization, and micturition. To control these behaviors the PAG depends on strong input from more rostrally located limbic structures, as well as from afferent input from the lower brainstem and spinal cord. Mouton and Holstege (2000, J Comp Neurol 428:389-410) showed that there exist at least five different groups of spino-PAG neurons, each of which is thought to subserve a specific function. The lateral cervical nucleus (LCN) in the upper cervical cord is not among these five groups. The LCN relays information from hair receptors and noxious information and projects strongly to the contralateral ventroposterior and posterior regions of thalamus and to intermediate and deep tectal layers. The question is whether the LCN also projects to the PAG. The present study in cat, using retrograde and anterograde tracing techniques, showed that neurons located in the lateral two-thirds of the LCN send fibers to the lateral part of the PAG, predominantly at rostrocaudal levels A0.6-P0.2. This part of the PAG is known to be involved in flight behavior. A concept is put forward according to which the LCN-PAG pathway alerts the animal about the presence of cutaneous stimuli that might represent danger, necessitating flight. J. Comp. Neurol. 471:434-445, 2004.

Animals↗
PubMed2004

The emotional brain: neural correlates of cat sexual behavior and human male ejaculation.

The organization of virtually all basic survival mechanisms in the central nervous system (CNS) is within the most central regions of the mesencephalon and the rostrally adjoining diencephalon; in particular, the mesencephalic periaqueductal gray (PAG) and hypothalamus. The PAG sends specific pathways to the caudal brainstem where neurons are located that, in turn, control nociception, blood pressure, heart rate, and micturition. Via projections to the nucleus retroambiguus (NRA) in the most caudal part of the medulla, the PAG controls the intra-abdominal pressure associated with vocalization, vomiting, and parturition. In cats, the PAG also controls sexual posture via NRA projections to motoneurons in the lumbosacral cord. These NRA-lumbosacral motoneuronal pathways are almost nine times stronger in the estrous vs. non-estrous female cat. While neuronal activity in specific CNS pathways is now known to control sexual behavior in the cat, how is it organized in the human? PET-scan results on human ejaculation have revealed that the meso-diencephalic transition zone is particularly and strongly activated. This region includes the so-called ventral tegmental area that is also known as a "reward area." For example, it is also activated during a heroin rush. Other strongly activated structures during sexual activity include the cerebellum and lateral part of the corpus striatum. At the level of the cerebral cortex, areas in the prefrontal and parietal cortex are also activated, but exclusively on the right side. Further study of these structures should certainly lead to better insight into human sexual behavior and provide the possibility to improve sexual activity in those who suffer from problems in this area.

Animals↗
PubMed2003

Brain activation during human male ejaculation.

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers. Manual penile stimulation was performed by the volunteer's female partner. Primary activation was found in the mesodiencephalic transition zone, including the ventral tegmental area, which is involved in a wide variety of rewarding behaviors. Parallels are drawn between ejaculation and heroin rush. Other activated mesodiencephalic structures are the midbrain lateral central tegmental field, zona incerta, subparafascicular nucleus, and the ventroposterior, midline, and intralaminar thalamic nuclei. Increased activation was also present in the lateral putamen and adjoining parts of the claustrum. Neocortical activity was only found in Brodmann areas 7/40, 18, 21, 23, and 47, exclusively on the right side. On the basis of studies in rodents, the medial preoptic area, bed nucleus of the stria terminalis, and amygdala are thought to be involved in ejaculation, but increased rCBF was not found in any of these regions. Conversely, in the amygdala and adjacent entorhinal cortex, a decrease in activation was observed. Remarkably strong rCBF increases were observed in the cerebellum. These findings corroborate the recent notion that the cerebellum plays an important role in emotional processing. The present study for the first time provides insight into which regions in the human brain play a primary role in ejaculation, and the results might have important implications for our understanding of how human ejaculation is brought about, and for our ability to improve sexual function and satisfaction in men.

Adult↗